DESCRIPTION: The human genome project (HGP) is developing databases of DNA sequences and gene maps that are expected to enhance the molecular understanding of normal physiological processes and disease pathology. Most biological processes, especially chronic diseases such as cancer, osteoporosis, and autoimmune diseases, arise from multiple interactions of genes with external factors including dietary constituents. Analyzing and understanding genotype x environment interactions has been difficult because of the complexity of factors and the complexity of the biological responses, which are unique to each individual. The approach proposed by the applicant combines an integrated biological system with an integrated technological system for examining complex genome-based responses in a defined murine model system. The working hypothesis underlying the biological strategy is that a subset of diet- regulated genes participate in disease processes in susceptible individuals. The integrated technological approach is based upon high throughput isolation, identification, and characterization of multiple genes using a novel, fluorescence-based capillary electrophoresis system. The long term goal is to identify and characterize genes regulated by diet and involved in disease processes in model systems in order to develop greater molecular understanding of nutrient- genotype interactions underlying human disease processes.